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Non-muscle invasive bladder cancer represents about 70% of all cases and has generally a favorable outcome. However, recurrence rates as high as 60 to 70% and progression rates of 10 to 20% necessitate intensive surveillance with cystoscopy. The invasiveness and high cost of cystoscopy poses significant burden on BC patients as well as on the healthcare system. In this study we test the feasibility of a simple, sensitive, and non-invasive detection of BC using Bladder CARE test in urine samples.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Urine from 136 healthy and 77 BC subjects was collected using the at-home Bladder CARE Urine Collection Kit and analyzed with Bladder CARE test. The test measures the methylation level of three BC-specific biomarkers and two internal controls using methylation-sensitive restriction enzymes coupled with qPCR. Bladder CARE showed an overall sensitivity of 93.5%, a specificity of 92.6%, and a PPV and NPV of 87.8% and 96.2%, respectively. Bladder CARE has an LOD as low as 0.046%, which equates to detecting 1 cancer cell for every 2,200 cells analyzed. We also provided evidence that bisulfite-free methods to assess DNA methylation, like Bladder CARE, are advantageous compared to conventional methods that rely on bisulfite conversion of the DNA.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Highly sensitive detection of BC in urine samples is possible using Bladder CARE. The low LOD of the test and the measurement of epigenetic biomarkers make Bladder CARE a good candidate for the early detection of BC and possibly for the routine screening and surveillance of BC patients. Bladder CARE and the at-home urine sample collection system have the potential to (1) reduce unnecessary invasive testing for BC (2) reduce the burden of surveillance on patients and on the healthcare system, (3) improve the detection of early stage BC, and (4) allow physicians to streamline the monitoring of patients.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13148-021-01029-1","type":"journal-article","created":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T09:12:04Z","timestamp":1618996324000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Clinical evaluation of Bladder CARE, a new epigenetic test for bladder cancer detection in urine samples"],"prefix":"10.1186","volume":"13","author":[{"given":"Paolo","family":"Piatti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yap Ching","family":"Chew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiko","family":"Suwoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taikun","family":"Yamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Jara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi-Yu","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saum","family":"Ghodoussipour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siamak","family":"Daneshmand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamed","family":"Ahmadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Rice","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Bhasin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faith","family":"Holloway","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshitomo","family":"Chihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8664-922X","authenticated-orcid":false,"given":"Gangning","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,4,21]]},"reference":[{"key":"1029_CR1","doi-asserted-by":"publisher","first-page":"5","DOI":"10.3322\/caac.21254","volume":"65","author":"RL Siegel","year":"2015","unstructured":"Siegel RL, Miller KD, Jemal A. 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Each healthy volunteer subject participating to this study signed a consent form provided by Zymo Research Corp. and approved by an internal committee. Urine from bladder cancer patients were collected in accordance with IRB-approved protocols at the Department of Urology, USC Norris Comprehensive Cancer Center (Los Angeles, CA, USA), and at Geneticist Inc. (Glendale, CA, USA).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"G. Liang certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject of matter or materials discussed in the manuscript (e.g., employment\/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patent applications that are pending or issued as patents), are the following: P. Piatti is named, along with W. Guo, X.Y. Jia (Jia), and G. Liang in US and foreign equivalent pending patent applications and issued patents for \u201cAssays to Determine DNA Methylation and DNA Methylation Markers of Cancer\u201d held by Zymo Research Corp. an associate of Pangea Laboratory, LLC. X.Y. Jia is an employee at Zymo Research Corp. and Pangea Laboratory, LLC. Dr. P. Piatti, Dr. Y.C. Chew, M. Suwoto, and T. Yamada are employees at Zymo Research Corp. and independent contractors with Pangea Laboratory, LLC. The remaining authors have nothing to disclose.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"84"}}